Malignant gliomas remain among the most refractory malignancies, causing significant functional deficits and high mortality in patients. Median survival is still measured in weeks, and fewer than 5% of patients diagnosed with the most common subtype, glioblastoma multiforme, are alive at five years. Notwithstanding the fact that this is an orphan indication with only 20,000-25,000 new cases annually, the impact belies the numbers. Furthermore, despite 20 years of active clinical trials, these median survival numbers have barely changed. The gap, it appears, is in the lack of novel therapeutics for early-phase clinical testing. Recently, the NCI supported two brain tumor Specialized Programs in Research Excellence (SPOREs), each affiliated with one of two brain tumor consortia, University of Alabama Birmingham (UAB) with New Advances in Brain Tumor Therapy (NABTT), and University of California San Francisco (UCSF) with the North American Brain Tumor Consortium (NABTC). Even these SPORE programs are limited in their ability to provide the critical product development and for-profit support to move novel strategies directly into the clinic and beyond. This AP4 application seeks to directly address translational, commercializable research with a specific focus on late-stage pre-clinical therapeutics and direct translation into IND agents for pilot clinical studies. We will take advantage of a number of novel approaches from our center researchers including a highly novel cellular therapy platform (Chopp), promising agents from the UAB SPORE program (Rosenfeld), and generate new contacts for future "drugable" targets towards glioma invasion and angiogenesis, areas in which our two academic groups have distinguished themselves. We will have available the resources from the NCI/NINDS Neuro-oncology Branch, with whom we have an ongoing collaboration for expression profiling and target assessment in clinical material (NCI/NINDS Fine) and the computation and screening capabilities from TGen, the Translational Genomics Institute (Berens). These discoveries will be assessed and developed for commercialization though partnership with corporate entities experienced in drug development and financing strategies, including Toucan Capital Corn. (Ms. Powers) and two of its portfolio companies: Oncocidex (Dr. Herring) and Cognate Therapeutics (Dr. Gordon). This Center will capture the entrepreneurial spirit from these diverse but complementary players, all highly motivated in the core mission, expanding the pipeline of novel therapeutics and diagnostics for malignant glioma patients.